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Interior Cancer Journal

An Adjuvant Therapy, Plerixafor, Shows Promise in the Treatment of Glioblastoma Multiforme

In late summer of 2013, a 66-year-old man living in Panama developed vision difficulties, a persistent right-sided headache and memory loss for recent events. When a CT of the brain performed in Panama City revealed a large right temporal occipital tumor, the patient sought care in Houston, where he was diagnosed with glioblastoma multiforme (GBM), a tumor notorious for its poor prognosis and short clinical history. The average length of survival following diagnosis is 12 to 15 months.

Adan Rios“It’s almost a given that patients who receive the standard-of-care treatment for GBM – maximal resection of the tumor, intensive radiation therapy and chemotherapy with temozolomide – will suffer a relapse,” says Adan Rios, M.D., an associate professor in the division of Oncology at McGovern Medical School at UTHealth and a member of the medical staff at Memorial Hermann-Texas Medical Center. “As a result, there is a generalized very fatalistic attitude toward GBM, much the same as we once had about other diseases that are now curable. The propensity of the tumor to recur and cause death has long been a difficult oncological problem, especially when viewed in light of the intensity of the treatment. As researchers, we continue to seek treatments that will produce good responses, with an eye toward developing a cure.”

In a case report published in May 2016 in Oncoscience,1 Dr. Rios and other authors at McGovern Medical School reported the results of adding plerixafor to the standard-of-care regimen as an adjuvant therapy. “Preclinical studies in a human xenograft animal model2 have shown us that the standard-of-care treatment kills the tumor cells and the blood vessels that supply the tumor. However, after treatment, there’s an increase in the tumor cavity of a factor known as stromal derived factor 1 (SDF-1), the cognate ligand of the CXCR4 receptor,” he says. “This increase produces mobilization of CXCR4 + myeloid cells from the bone marrow and the circulatory system. Once these cells attracted by the SDF-1 recolonize the tumor cavity, they produce secondary blood vessels (vasculogenesis) that renourish the dying tumor. We hypothesized that, if we treated our patients in a similar manner as was done in the animal model and could block these cells to keep them from rescuing the tumor, either the cancer would be cured or the period of response to the therapy would be increased significantly. Rather than seeking a new treatment that might do a better job of destroying the tumor itself, patients with GBM may benefit more from a therapy that allows the standard treatment to continue its course and destroy the tumor without being subverted by the vessel-saving cells.”

That therapy may be plerixafor, an immunostimulant used to mobilize hematopoietic stem cells into the bloodstream in cancer patients. When the patient from Panama had completed his first 12 months of adjuvant treatment with plerixafor, his adjuvant regimen of temozolomide and lapatinib were discontinued. At the time of this publication, he was 36 months out from diagnosis – more than double the average life expectancy. His plerixafor regimen has been changed from weekly to once a month, and he continues on metformin and niacinamide, without clinical or radiological evidence of relapse.

“We recognize the limitations inherent in reporting only one case, but given the natural history of GBM, the duration of the patient’s response deserves attention,” Dr. Rios says. “To our knowledge, he is the first patient treated with an adjuvant regimen involving a combination of chemotherapy plus inhibitors of metabolic pathways – and more significantly, plerixafor, an agent that specifically inhibits vasculogenesis. Clinical observations of a disease with a very poor prognosis don’t require a large number of cases to demonstrate the effectiveness of a particular approach. The fact that our patient had a positive response – plus the positive results of studies in an animal model – makes adjuvant treatment with plerixafor of great interest to us.”

“It’s really exciting to think that the standard-of-care treatment for glioblastoma may just need a tweak," he adds. "In a disease notorious for fatal outcomes, any intervention that gives a patient longer life is worthy of further clinical exploration.”

1 Rios A, Hsu SH, Blanco A, Buryanek J, Day AL, McGuire MF, Brown RE. Durable response of glioblastoma to adjuvant therapy consisting of temozolomide and a weekly dose of AMD3100 (plerixafor), a CXCR4 inhibitor, together with lapatinib, metformin and niacinamide. Oncoscience. 2016 May;(3)5-6:156-63.

2 Kioi M., Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J. Clin. Invest. 2010;120(3):694-705.